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          <a class="brand" href="/maddamse">Rohan Maddamsetti</a>
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      <h1 id="big-questions">Big Questions</h1>

<p>I&#8217;m interested in many questions, including many things outside of my immediate expertise. I&#8217;m always looking for people to talk to about these ideas. I&#8217;d love to collaborate as well, if there&#8217;s something that I can contribute!</p>

<p>Broadly, I&#8217;m interested in understanding what the fundamental limits are in designing complex systems.</p>

<p>The industrial revolution allowed people to design systems of unprecedented complexity, such as airplanes, highways, the electric grid, and the Internet. These rapid changes in human development have put <a href="http://www.nature.com/nature/journal/v486/n7401/full/nature11148.html">tremendous stress on the natural ecological systems of which humanity has always been a part.</a> Climate change, desertification, pandemics, and access to finite resources like food, water, and energy now pose a threat to both <a href="http://rspb.royalsocietypublishing.org/content/280/1754/20122845.full.pdf+html">global civilization</a> and <a href="http://www.nature.com/nature/journal/v486/n7401/full/nature11018.html">natural ecosystems</a> as well know them.</p>

<p>Our global society, and economic system are naturally a part of the fabric of the greater ecological systems that encompass the biosphere. <a href="http://www.nature.com/nature/journal/v486/n7401/full/nature11157.html">Can people design better ways of integrating human systems, like cities, into the biosphere?</a> Or is this an impossible task? Are there fundamental limits on the controllability and predictability of how engineered systems can interface with natural systems?</p>

<p>As a biologist, I&#8217;m interested in understanding the limits to designing and building model organisms and ecologies. My hope is that my research will eventually help people develop effective responses to the myriad ecological challenges that humanity faces in the coming centuries.</p>

<h3 id="hard-limits-in-biology-what-is-the-design-space-of-biological-systems">Hard Limits in Biology: what is the design space of biological systems?</h3>

<p>I&#8217;ve read a few papers that attack this problem. Here are a couple more theoretically oriented papers: <a href="http://www.cds.caltech.edu/~doyle/wiki/images/7/71/CorrectedScienceGlycolyticOscOnlineFinal.pdf">Doyle et al.</a> and <a href="http://paulsson.med.harvard.edu/Web_pdfs/nature09333.pdf">Lestas et al.</a></p>

<p>I have a poor sense of the true limits that physics and chemistry place on the possible scope of biological systems. Living things have evolved under serious resource and energetic constraints. What kind of imaginary beings are biologically feasible, and what are not? For instance, <a href="http://irl.cs.ucla.edu/papers/right-size.html">a ten-story ant is unfeasible because it would collapse under it’s own weight.</a> But given the availability of unlimited energetic resources and metabolic building blocks, could one design a fire-breathing dragon, in principle, anyway?</p>

<p>Steve Benner has worked on understanding the possible chemical basis for life for a few decades now; <a href="http://www.ffame.org/pubs/Synthetic%20Biology%2C%20Tinkering%20Biology%2C%20and%20Artificial%20Biology%3A%20A%20Perspective%20from%20Chemistry.pdf">see this book chapter.</a></p>

<h3 id="the-limits-that-ecology-and-evolutionary-processes-place-on-synthetic-biology">The Limits that Ecology and Evolutionary Processes place on Synthetic Biology</h3>

<p>The main characteristic of biological systems is self-reproduction. Reproduction entails errors, or mutations. This means that designed biological systems can break down due to accumulated mutations, or due to natural selection for unintended behaviors. Genetic changes in a population cause changes in the environment in which the population lives, and these inevitable ecological changes can then feedback onto how the population evolves next. Stochastic and unpredictable changes in biological systems due to evolution and ecological changes are a given. How well can synthetic organisms and communities be designed and controlled, due to these limitations? Two papers that inspired some of these thoughts are the following: <a href="http://www.biomedcentral.com/content/pdf/gb-2006-7-8-114.pdf">Arkin et al.</a> and <a href="https://www.sciencemag.org/content/309/5731/137.full.pdf">Balagadde et al.</a></p>

<h3 id="using-synthetic-biology-to-study-the-evolutionary-process">Using synthetic biology to study the evolutionary process</h3>

<p>Engineering new genomes allows us to ask “what-if” questions about evolution. <a href="http://arxiv.org/abs/1209.5032">This paper</a> is a good example of this.</p>

<h3 id="bioprospecting-and-biodiversity">Bioprospecting and Biodiversity</h3>

<p>One selfish reason for preserving biodiversity, is that living things are an incredible resource for developing new drugs, foods, and technologies. Genetic engineering is <a href="http://en.wikipedia.org/wiki/Neolithic_Revolution">the fundamental technology that allowed civilization to develop.</a></p>

<p>Given how endangered global ecosystems are, I’m interested in bioprospecting as one capitalist mechanism for preserving what wilderness we have left.</p>

<h3 id="speciation-and-tradeoffs-in-design-space">Speciation and tradeoffs in design space</h3>

<p>Why do so many species exist? I’m interested in understanding how fundamental (as opposed to accidental) tradeoffs in phenotypic, or design space, result in the many different kinds of living things that exist. In the Lenski lab, Zachary Blount’s research program is largely centered on these issues.</p>

<h3 id="multi-level-selection">Multi-level selection</h3>

<p>I’m interested in theoretical approaches to evolution that explicitly incorporate multi-level processes, and frequency-dependence. These include adaptive dynamics, and evolutionary game theory. Furthermore, I’m interested in multi-level selection as a mechanism for controlling, building and maintaining desired communities, organisms, and phenotypes that may not be selectively beneficial on a lower level of selection. I first became familiar with these theoretical approaches from reading Sean Rice’s excellent <a href="http://www.amazon.com/Evolutionary-Theory-Sean-H-Rice/dp/0878937021/">Evolutionary Theory</a>. I&#8217;ve also encountered several papers in the literature that deal with these issues, such as the following: <a href="http://lac-repo-live7.is.ed.ac.uk/bitstream/1842/469/1/Kiers_etal_03.pdf">Kiers et al.</a>, <a href="http://www.sciencemag.org./content/323/5911/272.short">Chuang et al.</a>, <a href="http://gorelab.homestead.com/HostMovesFirst.pdf">Damore and Gore</a>, <a href="http://gorelab.homestead.com/files/QuickSiteImages/SnowdriftGameYeastNature.pdf">Gore et al.</a>, <a href="http://onlinelibrary.wiley.com/doi/10.1002/bies.200900182/abstract">Wooldridge 2010</a>, and <a href="http://gorelab.homestead.com/Velenich_CurrOpinionChemBio_2012.pdf">Velenich et al.</a></p>

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